ibogaine (DMX-1002) / atai Life Sci - LARVOL DELTA

atai Life Sciences Reports Second Quarter 2023 Financial Results and Operational Highlights, and Announces Clinical Data from the Phase 1 Study of DMX-1002 (Ibogaine) (GlobeNewswire) - P1/2 | N=116 | NCT05029401 | Sponsor: DemeRx IB, Inc.| "atai Life Sciences...reported second quarter 2023 financial results and provided corporate updates...Today, the company announced results from the Phase 1 study of DMX-1002, a cholinergic, glutamatergic and monoaminergic receptor modulator being developed for the treatment of OUD...Results of the Phase 1 trial demonstrated that oral doses of DMX-1002 at 9 mg/kg achieved plasma concentrations in line with those described in previous studies in which subjects reported psychedelic experiences and obtained therapeutic benefit in OUD...The on-going Phase 2b study...of RL-007 vs placebo...The company expects to report topline results from this study in the 2nd half of 2024...on-going Phase 1 study...of VLS-01...The company expects to report additional clinical data in Q3 2023."

P1 data • P1/2 data • P2b data • Cognitive Disorders • Schizophrenia

Reply to Knuijver et al., on the "Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study". (PubMed, Addiction) - No abstract available

Clinical • Journal • Observational data • Addiction (Opioid and Alcohol) • Ataxia • Movement Disorders

A Study of Oral Ibogaine in Opioid Withdrawal (clinicaltrials.gov) - P1/2; N=110; Recruiting; Sponsor: DemeRx IB, Inc.

Clinical • New P1/2 trial

Evaluating the toxicity and therapeutic potential of ibogaine in the treatment of chronic opioid abuse. (PubMed, Expert Opin Drug Metab Toxicol) - No abstract available

Journal • Substance Abuse

Safety of ibogaine administration in detoxification of opioid dependent individuals: a descriptive open-label observational study. (PubMed, Addiction) - "An open-label observation study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia."

Clinical • Journal • Observational data • Addiction (Opioid and Alcohol) • Ataxia • Cardiovascular • CNS Disorders • Movement Disorders • Psychiatry

Death due to consumption of ibogaine: case report. (PubMed, Forensic Sci Med Pathol) - "Moreover, systematic toxicological analyses of biological samples showed the presence of morphine and codeine. These data suggest that death, which occurred unnaturally after initiation of the "treatment", was probably the result of the cardiovascular effects caused by the ibogaine powder.The presented case highlights the worldwide problem of various products being widely available over the internet and the danger associated with consumption thereof."

Clinical • Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Psychiatry • Respiratory Diseases • Substance Abuse

Rapid synthesis of azepinoindole derivatives from tryptamine sulfonamides and bromoallyl sulfones via an acid-mediated cyclization and rearrangement. (PubMed, Chem Commun (Camb)) - "The azepinoindole framework present in natural alkaloids such as subincanadine F, ibogaine and catharanthine was formed in a novel acid-promoted cyclization-rearrangement of tryptamine-derived N-sulfonyl enamines...The azepinoindole forming cyclization-rearrangement involves the initial generation of a six-membered tetrahydro-β-carboline derivative. The steric bulk of the N-sulfonyl group on tryptamine plays an important role in deciding the reaction outcome."

Journal

A non-hallucinogenic psychedelic analogue with therapeutic potential. (PubMed, Nature) - "The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals...In rodents, tabernanthalog was found to promote structural neural plasticity, reduce alcohol- and heroin-seeking behaviour, and produce antidepressant-like effects. This work demonstrates that, through careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Atrial Fibrillation • Cardiovascular • CNS Disorders • Depression • Psychiatry

Preliminary Efficacy and Safety of Ibogaine in the Treatment of Methadone Detoxification (clinicaltrials.gov) - P2; N=20; Recruiting; Sponsor: International Center for Ethnobotanical Education, Research, and Service; Not yet recruiting ➔ Recruiting; Trial completion date: Sep 2021 ➔ Sep 2022; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Biosynthesis of an Anti-Addiction Agent from the Iboga Plant. (PubMed, J Am Chem Soc) - "Notably, (-)-ibogaine and (-)-voacangine are of the opposite enantiomeric configuration compared to the other major alkaloids found in this natural product class. Therefore, this discovery provides insight into enantioselec-tive enzymatic formal Diels-Alder reactions."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies. (PubMed, CNS Drugs) - "This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders."

Clinical • Journal • Review • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

[VIRTUAL] Iboga alkaloids as inspiration for plasticity-promoting neurotherapeutics (ACS-Fall 2020) - "Strategies for the total synthesis of iboga alkaloids and function-oriented synthesis of ibogaine congeners will be discussed. Iboga alkaloids have inspired our medicinal chemistry efforts to develop safer and more effective neurotherapeutics, and they serve as key chemical tools in our studies to understand the fundamental biochemical mechanisms that give rise to neural plasticity."

CNS Disorders • Depression • Mental Retardation • Psychiatry

The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs. (PubMed, Nat Prod Rep) - "This family of monoterpenoid indole alkaloids includes the anti-addictive compound ibogaine as well as catharanthine, a precursor to the chemotherapeutic vinblastine. Whenever appropriate, we provide historical context for the discoveries of the past decade and indicate areas that have yet to be resolved. While significant progress regarding their chemistry and pharmacology has been made since the 1960s, it is clear that the iboga alkaloids will continue to stoke scientific innovation for years to come."

Journal • Review • CNS Disorders • Psychiatry

Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans. (PubMed, Chronic Stress (Thousand Oaks)) - "Therefore, this study examined psychedelic treatment with ibogaine and 5-methoxy-N,N-dimethyltryptamine for trauma-related psychological and cognitive impairment among U.S. Special Operations Forces Veterans...Psychedelic-assisted therapy with these under-researched psychedelics may hold unique promise for this population. However, controlled studies are needed to determine whether this treatment is efficacious in relieving mental health and cognitive impairment among U.S. Special Operations Forces Veterans."

Journal • Alzheimer's Disease • CNS Disorders • Depression • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Suicidal Ideation

Ibogaine therapy for addiction: Consumer views from online fora. (PubMed, Int J Drug Policy) - "Fora discussions illustrate that neuroscientific explanations of addiction and behaviour have explanatory salience for people involved in ibogaine therapy. Online fora could be used as a platform for clinician and peer-led support and harm-reduction interventions, and for further research monitoring treatment practices and long-term outcomes."

Journal • CNS Disorders

Ibogaine Consumption With Seizure-Like Episodes, QTc-Prolongation, and Captured Cardiac Dysrhythmias. (PubMed, J Emerg Med) - "Qualitative analysis confirmed the presence of ibogaine in the empty foil packages containing the ingested substance. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As increasing numbers of opioid-dependent patients attempt to curtail their substance use disorders, we anticipate a rise in ibogaine exposures, necessitating awareness by front-line clinicians in recognizing and treating a drug exposure that can rapidly become life-threatening."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Epilepsy

Substrate and inhibitor binding to the serotonin transporter: insights from computational, crystallographic, and functional studies. (PubMed, Neuropharmacology) - "Herein, we aim to highlight and compare these studies with an emphasis on what the different experimental methods conclude on substrate and inhibitor binding modes, and the potential caveats of using the different types of studies are discussed. We focus this review on the binding of cognate substrate and drugs belonging to the different families of antidepressants, including tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and multimodal drugs, as well as illicit drugs such as cocaine, amphetamines, and ibogaine."

Journal • Review • CNS Disorders • Depression • Mood Disorders • Psychiatry

Preliminary Efficacy and Safety of Ibogaine in the Treatment of Methadone Detoxification (clinicaltrials.gov) - P2; N=20; Not yet recruiting; Sponsor: International Center for Ethnobotanical Education, Research, and Service; Trial completion date: Dec 2020 ➔ Sep 2021

Clinical • Trial completion date • Addiction (Opioid and Alcohol)

Hallucinogens and Their Therapeutic Use: A Literature Review. (PubMed, J Psychiatr Pract) - "The results showed that a variety of substances have been evaluated in the treatment of psychiatric disorders, including ayahuasca, ibogaine, ketamine, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, and psilocybin. However, it was difficult to draw definitive conclusions as most studies suffered from small sample sizes, inconsistent measures, and poor study design. To properly assess the risks and potential benefits of hallucinogens in psychiatric treatment, there is a need for well designed, standardized studies that demonstrate the impact of hallucinogenic substances on psychiatric conditions."

Journal • Autism Spectrum Disorder • CNS Disorders • Depression • Genetic Disorders • Psychiatry

Neurotrophic mechanisms of psychedelic therapy (PubMed, Biol Aujourdhui) - "Since the discovery of ketamine antidepressant effects, there has been growing interest for these molecules. Serotonergic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) are gaining attention as potential treatments for depression and addiction, similarly to 3,4-methylenedioxymethamphetamine (MDMA) for post-traumatic stress disorder (PTSD), and ibogaine for addiction...Finally, we show how ibogaine could exert its anti-addictive properties through a completely different neurotrophic factor than other psychedelic drugs, the glial cell line-derived neurotrophic factor (GDNF). While the current literature concerning the psychiatric applications of psychedelic therapy is encouraging, it remains to be determined whether their benefits could be obtained without their psychotomimetic effects, or concerns over potential toxicity."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mood Disorders • Post-traumatic Stress Disorder

Ibogaine and Subjective Experience: Transformative States and Psychopharmacotherapy in the Treatment of Opioid Use Disorder. (PubMed, J Psychoactive Drugs) - "Many participants reported feeling a sense of spiritual transformation. We propose that the reported experiences support the meaningfulness of ibogaine's oneiric effects as a discrete element in its capacity for healing, which is distinct from pharmacological actions associated with reduced withdrawal and craving."

Clinical • Journal • Addiction (Opioid and Alcohol)

On Addiction, Complexity, and Freedom: Toward a Liberation-Focused Addiction Treatment. (PubMed, J Psychoactive Drugs) - "Examples of how biomedical, psychological, and social interventions can each serve to promote the goal and experience of freedom and liberation are provided. Engaging in identity projects and using harm reduction interventions and philosophies are also seen as key to this transformative journey."

Journal • Addiction (Opioid and Alcohol)

Antimycobacterial Activity of Alkaloids and Extracts from Tabernaemontana alba and T. arborea. (PubMed, Planta Med) - "We therefore screened alkaloid extracts obtained from the root and stem barks of the Mexican Apocynaceae species Tabernaemontana alba and Tabernaemontana arborea, as well as the pure alkaloids ibogaine, voacangine, and voacamine, tested for activity against Mycobacterium tuberculosis H37Rv and cytotoxicity to mammalian Vero cells using the resazurin microtiter and the MTT assays, respectively...However, all of these compounds showed cytotoxicity to Vero cells, with a poor selectivity index of 1.00, 0.16, and 1.42, respectively. This is the first report of voacamine activity against M. tuberculosis."

Journal • Infectious Disease • Tuberculosis

A Single Administration of the Atypical Psychedelic Ibogaine or its Metabolite Noribogaine Induces an Antidepressant-like Effect in Rats. (PubMed, ACS Chem Neurosci) - "At this time point, both ibogaine and noribogaine were present in rat brain at concentrations that cannot produce the same behavioral outcome on their own (ibogaine ~ 0.5 M, noribogaine ~ 2.4 M). Our data suggests a polypharmacological mechanism underpinning the antidepressant-like effects of ibogaine and noribogaine."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry • BDNF

[VIRTUAL] Ibogaine in the Treatment of Substance Use Disorders (EPA 2020) - No abstract available